Gail Underbakke

Putting the Diabetes Prevention Program into practice: a program for weight loss and cardiovascular risk reduction for patients with metabolic syndrome or type 2 diabetes mellitus.

Background: The increasing incidence and prevalence of metabolic syndrome and type 2 diabetes mellitus (DM) have significant implications on health world-wide. Large clinical trials have demonstrated the effectiveness of a comprehensive lifestyle program with a goal of moderate weight loss (5–7%) and regular exercise (150 minutes/week), resulting in a significant decrease in the incidence of type 2 DM and cardiovascular risk.Methods: This study reports on the translation of the multi-center Diabetes Prevention Program (DPP) into a cardiac rehabilitation program, utilizing the expertise and experience of a cardiac rehabilitation program staff. The study adapted materials from the DPP to develop a program that fit local needs for diabetes prevention.Results: Most participants completed the program (11 months) and their moderate weight loss was maintained for 11–12 months. At 11–12 months, waist circumference was reduced by approximately 2 inches, percent body fat was reduced by 5% (11% relative decrease, p<.05), weight was decreased by 10.1 pounds (p<.05), and blood pressure was reduced 8/3 mm Hg (p<.05). Exercise, nutrition, glucose, triglycerides, LDL-cholesterol and HDLcholesterol were all were significantly improved at 11–12 months (p<.05).Conclusions: Efforts to improve lifestyle and reduce body weight are important to patients at risk of developing diabetes. This program demonstrates that an intensive effort can significantly improve lifestyle and reduce body weight in patients with DM or at risk for DM. A program that simulates cardiac rehabilitation, translated from a successful clinical trial into practice, resulted in significant reduction and improvement in metabolic outcomes and cardiovascular risk. Support for cardiac rehabilitation from insurers to develop similar programs is encouraged and deserves further study.

Nonresponse bias: Does it affect measurement of clinician behavior?

Background.Previous studies of nonresponders have not assessed the effects of nonresponse on the accuracy of clinician behavior measurements. Knowledge of these effects is critical to both research and quality improvement. Objective.To evaluate the hypothesis that nonresponders to a survey would not adversely affect the ability to measure rates of preventive services. Research Design.Four primary-care medical practices participating in a randomized clinical trial provided an unusual opportunity to compare the medical record-documented care of both responders and nonresponders to a survey of their patients. Subjects. Three hundred forty-five nonresponders and 321 responders to a questionnaire requesting participation in the study. Measures. Differences in patient characteristics and diseases and documentation of screening and management of tobacco use, hypertension, and hypercholesterolemia. Results. Although the survey process resulted in a response rate of only 52.5% and some statistically significant differences in responder and nonresponder characteristics, there were no differences in management behavior regarding cardiovascular risk factors. Responders were more likely to have adjusted documentation of tobacco use (OR = 1.4), blood pressure measurement (OR = 9.8), and cholesterol testing (OR = 2.0), but not family history of cardiovascular disease. The most striking difference in subject characteristics was that 22.0% of nonresponders and only 12.1% of responders were tobacco users (P = 0.002). Conclusions. This study confirms that survey nonresponders may have some different characteristics and risk factor screening rates than responders. However, if confirmed by others, nonresponders who have risk factors identified may not be managed differently than responders.

The Effects of Ramipril in Individuals at Risk for Alzheimer’s Disease: Results of a Pilot Clinical Trial

Research shows that certain antihypertensives taken during midlife confer Alzheimers disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-β (Aβ) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE ε4 carriers. While results did not show a treatment effect on CSF Aβ(1-42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Aβ1-42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine.

882-3 Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors

BACKGROUND Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs. METHODS This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning. RESULTS At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 +/- 180 nmol/L), which tended to be small (19.9 +/- 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 +/- 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 +/- 0.58 mmol/L). FMD was impaired (4.5% +/- 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P =.030), a 26.7% reduction in small LDL (P =.100), and a 44.9% reduction in small VLDL (P =.023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% +/- 0.6%); however, the difference between treatment phases was not statistically significant (P =.080). CONCLUSIONS This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.